What should doctors do when patients have “incidental” findings of important variants related to cardiovascular disease? This is an increasingly important question as genome screens become more common both in the clinic and on the consumer market.
A new scientific statement, published today in Circulation: Genomic and Precision Medicine, aims to help clarify what clinicians should do when such variants are uncovered, but not as part of a cardiovascular disease workup.
The authors note there are currently 42 secondary variant genes that increase the risk of sickness or death from treatable conditions such as sudden cardiac death and heart failure. This statement, they say, is the first to focus on inherited monogenic, or single-gene, diseases that can be passed on within families, such as hypertrophic cardiomyopathy or long QT syndrome.
“If we interpret these incidental variants incorrectly, it may lead to inappropriate care, either by suggesting patients have a risk of cardiac disease when they do not, or by not providing care to those with increased risk for a serious condition,” says Andrew P. Landstrom, MD, PhD, FAHA, chair of the scientific statement writing committee and associate professor of pediatrics and cell biology at Duke University School of Medicine.
The new statement, “Interpreting Incidentally Identified Variants in Genes Associated with Heritable Cardiovascular Disease,” suggests next steps to determine whether a variant truly carries a health risk, advises health care professionals on how to communicate with people and their families, and suggests appropriate follow-up actions to care when variants are uncovered.
To start, pre-test genetic counseling is strongly encouraged to prepare patients for the possibility of incidental findings, how and whether these findings will be communicated, and potential implications for themselves and family members.
Once an incidental genetic variant for cardiovascular disease is found, the authors suggest a framework for interpreting the variant and determining whether it is classified as benign, uncertain, or pathogenic (disease-causing):
- Health care professionals should only relay information to patients about incidentally identified variants if they are among the cardiovascular disease genes already known to be associated with CVD and if patients agreed during pretest genetic counseling to be informed about incidental findings.
- Incidentally identified variants in genes with an uncertain association with heart disease should not be reported.
- If the discovered variant may increase the risk of heart disease, a family history and medical evaluation by an expert health care professional are suggested. The goal of this evaluation is to determine whether the individual has evidence of the disease, such as symptoms or relevant test results, or if there are any warning signs in the family history.
- The genetic variant itself should be re-evaluated periodically by an expert or expert team to ensure whether its status has changed.
- Finally, the medical evaluation and genetic re-evaluation should guide next steps, which may vary from dismissing the incidental variant not likely to raise risk or starting medical interventions. This process may also involve periodic re-evaluation with appropriate tests (echocardiogram, blood tests, etc.) and possibly screening other family members for the variant.
“The list of incidental variants related to cardiovascular disease continues to evolve. This statement provides a foundation of care that may help people with a CVD-related genetic variant and their health care professionals take the next step in determining the individual and familial risk that a variant may or may not carry,” Landstrom said.
“It’s also important to consult with genetics specialists to custom-tailor an evaluation and treatment plan to both the individual and the genetic variant in order to ensure the highest level of care possible,” he added.